We plan to study development of anatomical aspects of the auditory system relevant to binaural interaction using the ferret as a model. Our overall goal is to determine how central auditory neurons develop the appropriate binaural interactions to code the location of a sound source. We have chosen the ferret because of its similarity to the cat, which has been the dominant animal in anatomical, electrophysiological, and behavioral studies of binaural interaction and because of the immaturity of the ferret nervous system at birth. In establishing a model of development of bineural interaction, we will begin by collecting baseline data in the adult and developing ferret. In the adult ferret, it is not our aim to simply reiterate work on auditory organization in other species. Rather, baseline data on the ferret auditory system will be collected while addressing unanswered questions in binaural organization using electron microscopy and tract-tracing techniques. In the neonatal ferret we will use the same techniques as in the adult, as well as the Golgi method and techniques to quantify normally-occurring cell death to study the development of auditory nuclei involved in binaural interaction and their interrelationships. Our main focus will be the two primary binaural nuclei, the medial and lateral superior olivary nuclei; the target of those two nuclei, the inferior colliculus; and their source of input which is also a source of binaural input to the inferior colliculus, the cochlear nuclei. Having baseline data on specific features of binaural organization in the adult ferret and specific events in the development of nuclei concerned with binaural interaction, we will be able to ask more sophisticated questions on the development of binaural interaction. Understanding some of the basic mechanisms involved in the development of appropriate binaural interactions will be useful in appreciating the impact and consequences of numerous clinical conditions. Intrauterine infections such as rubella and cytomegaloviurs; genetic anomalies such as Hurler's and Waardenburg's syndromes; as well as birth trauma, anoxia, and maternal consumption of ototoxic drugs such as neomycin and ethacrynic acid all have deleterious effects on the developing auditory system. Information on the development of normal anatomical interrelationships may provide clues to the effects that these conditions may have on the development of auditory processing.